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Protein

Peptidyl-prolyl cis-trans isomerase FKBP5

Gene

FKBP5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Immunophilin protein with PPIase and co-chaperone activities. Component of unligated steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). Plays a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors maintaining the complex into the cytoplasm when unliganded.

Catalytic activityi

Peptidylproline (omega=180) = peptidylproline (omega=0).

Enzyme regulationi

Inhibited by FK506 but not cyclosporin.

GO - Molecular functioni

  • FK506 binding Source: ProtInc
  • heat shock protein binding Source: UniProtKB
  • peptidyl-prolyl cis-trans isomerase activity Source: UniProtKB

GO - Biological processi

  • chaperone-mediated protein folding Source: UniProtKB
  • protein folding Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Chaperone, Isomerase, Rotamase

Names & Taxonomyi

Protein namesi
Recommended name:
Peptidyl-prolyl cis-trans isomerase FKBP5 (EC:5.2.1.8)
Short name:
PPIase FKBP5
Alternative name(s):
51 kDa FK506-binding protein
Short name:
51 kDa FKBP
Short name:
FKBP-51
54 kDa progesterone receptor-associated immunophilin
Androgen-regulated protein 6
FF1 antigen
FK506-binding protein 5
Short name:
FKBP-5
FKBP54
Short name:
p54
HSP90-binding immunophilin
Rotamase
Gene namesi
Name:FKBP5
Synonyms:AIG6, FKBP51
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:3721. FKBP5.

Subcellular locationi

GO - Cellular componenti

  • endoplasmic reticulum membrane Source: GO_Central
  • extracellular exosome Source: UniProtKB
  • membrane Source: UniProtKB
  • nucleoplasm Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

MalaCardsiFKBP5.
PharmGKBiPA28162.

Chemistry

ChEMBLiCHEMBL2052031.

Polymorphism and mutation databases

BioMutaiFKBP5.
DMDMi2851536.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 457457Peptidyl-prolyl cis-trans isomerase FKBP5PRO_0000075324Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineCombined sources
Modified residuei13 – 131PhosphoserineCombined sources
Modified residuei445 – 4451PhosphoserineCombined sources

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ13451.
PaxDbiQ13451.
PeptideAtlasiQ13451.
PRIDEiQ13451.

PTM databases

iPTMnetiQ13451.
PhosphoSiteiQ13451.
SwissPalmiQ13451.

Expressioni

Tissue specificityi

Widely expressed, enriched in testis compared to other tissues.

Inductioni

By androgen.

Gene expression databases

BgeeiENSG00000096060.
CleanExiHS_FKBP5.
GenevisibleiQ13451. HS.

Organism-specific databases

HPAiCAB009315.
HPA031092.
HPA031093.
HPA031095.

Interactioni

Subunit structurei

Part of a heteromultimeric cytoplasmic complex with HSP90AA1, HSPA1A/HSPA1B and steroid receptors. Upon ligand binding dissociates from the complex and FKBP4 takes its place. Interacts with functionally mature heterooligomeric progesterone receptor complexes along with HSP90 and TEBP.

Binary interactionsi

WithEntry#Exp.IntActNotes
Q9WMX24EBI-306914,EBI-9005440From a different organism.
CDK15Q96Q402EBI-306914,EBI-1051975
CDK9P507504EBI-306914,EBI-1383449
CHUKO151112EBI-306914,EBI-81249
STK11Q158314EBI-306914,EBI-306838
USP49Q70CQ12EBI-306914,EBI-2511022

GO - Molecular functioni

  • heat shock protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi108579. 106 interactions.
DIPiDIP-27597N.
IntActiQ13451. 117 interactions.
MINTiMINT-1142816.
STRINGi9606.ENSP00000338160.

Chemistry

BindingDBiQ13451.

Structurei

Secondary structure

1
457
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi16 – 216Combined sources
Beta strandi22 – 243Combined sources
Beta strandi26 – 283Combined sources
Beta strandi30 – 3910Combined sources
Beta strandi42 – 443Combined sources
Beta strandi52 – 6110Combined sources
Beta strandi66 – 694Combined sources
Helixi70 – 734Combined sources
Beta strandi77 – 804Combined sources
Beta strandi83 – 864Combined sources
Helixi88 – 947Combined sources
Beta strandi102 – 1076Combined sources
Helixi109 – 1113Combined sources
Turni112 – 1165Combined sources
Turni119 – 1213Combined sources
Beta strandi128 – 13811Combined sources
Beta strandi144 – 15411Combined sources
Beta strandi167 – 17610Combined sources
Beta strandi179 – 18911Combined sources
Helixi193 – 1964Combined sources
Helixi200 – 2067Combined sources
Beta strandi214 – 2196Combined sources
Helixi221 – 2233Combined sources
Helixi231 – 2333Combined sources
Beta strandi241 – 25111Combined sources
Helixi256 – 2583Combined sources
Helixi261 – 28020Combined sources
Helixi284 – 29815Combined sources
Helixi306 – 32924Combined sources
Helixi333 – 34614Combined sources
Helixi351 – 36313Combined sources
Helixi367 – 37812Combined sources
Helixi387 – 41125Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1KT0X-ray2.70A1-457[»]
3O5DX-ray4.00A/B1-260[»]
3O5EX-ray1.60A1-140[»]
3O5FX-ray1.65A1-140[»]
3O5GX-ray2.00A16-140[»]
3O5IX-ray1.80A/B16-140[»]
3O5JX-ray1.70A16-140[»]
3O5KX-ray2.70A/B/C/D16-140[»]
3O5LX-ray1.30A16-140[»]
3O5MX-ray1.60A/B16-140[»]
3O5OX-ray1.15A16-140[»]
3O5PX-ray1.00A16-140[»]
3O5QX-ray0.96A16-140[»]
3O5RX-ray1.10A16-140[»]
4DRHX-ray2.30A/D1-140[»]
4DRIX-ray1.45A1-140[»]
4DRKX-ray1.50A/B16-140[»]
4DRMX-ray1.48A16-140[»]
4DRNX-ray1.07A16-140[»]
4DROX-ray1.10A16-140[»]
4DRPX-ray1.80A16-140[»]
4DRQX-ray1.00A16-140[»]
4JFIX-ray1.05A16-139[»]
4JFJX-ray1.08A16-140[»]
4JFKX-ray1.15A16-140[»]
4JFLX-ray1.20A16-140[»]
4JFMX-ray1.02A16-140[»]
4R0XX-ray1.20A20-140[»]
4TW6X-ray1.40A16-140[»]
4TW7X-ray1.25A16-140[»]
4TX0X-ray1.03A16-140[»]
4W9OX-ray1.27A/E16-140[»]
4W9PX-ray1.50A/E16-140[»]
4W9QX-ray1.08A16-140[»]
5BXJX-ray1.24A16-140[»]
5DITX-ray2.25A16-140[»]
5DIUX-ray1.30A16-140[»]
5DIVX-ray1.65A16-139[»]
ProteinModelPortaliQ13451.
SMRiQ13451. Positions 13-412.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13451.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini42 – 13089PPIase FKBP-type 1PROSITE-ProRule annotationAdd
BLAST
Domaini157 – 24387PPIase FKBP-type 2PROSITE-ProRule annotationAdd
BLAST
Repeati268 – 30134TPR 1Add
BLAST
Repeati317 – 35034TPR 2Add
BLAST
Repeati351 – 38434TPR 3Add
BLAST

Sequence similaritiesi

Contains 2 PPIase FKBP-type domains.PROSITE-ProRule annotation
Contains 3 TPR repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG0543. Eukaryota.
COG0545. LUCA.
GeneTreeiENSGT00760000119159.
HOGENOMiHOG000256916.
HOVERGENiHBG051624.
InParanoidiQ13451.
KOiK09571.
OMAiVCHLLCK.
OrthoDBiEOG091G07OA.
PhylomeDBiQ13451.
TreeFamiTF105292.

Family and domain databases

Gene3Di1.10.150.160. 1 hit.
1.25.40.10. 1 hit.
InterProiIPR023114. Elongated_TPR_rpt_dom.
IPR031210. FKBP5.
IPR023566. PPIase_FKBP.
IPR001179. PPIase_FKBP_dom.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR001440. TPR_1.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR10516. PTHR10516. 2 hits.
PTHR10516:SF26. PTHR10516:SF26. 2 hits.
PfamiPF00254. FKBP_C. 2 hits.
PF00515. TPR_1. 1 hit.
PF13181. TPR_8. 1 hit.
[Graphical view]
SMARTiSM00028. TPR. 2 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 1 hit.
PROSITEiPS50059. FKBP_PPIASE. 2 hits.
PS50005. TPR. 3 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13451-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTTDEGAKNN EESPTATVAE QGEDITSKKD RGVLKIVKRV GNGEETPMIG
60 70 80 90 100
DKVYVHYKGK LSNGKKFDSS HDRNEPFVFS LGKGQVIKAW DIGVATMKKG
110 120 130 140 150
EICHLLCKPE YAYGSAGSLP KIPSNATLFF EIELLDFKGE DLFEDGGIIR
160 170 180 190 200
RTKRKGEGYS NPNEGATVEI HLEGRCGGRM FDCRDVAFTV GEGEDHDIPI
210 220 230 240 250
GIDKALEKMQ REEQCILYLG PRYGFGEAGK PKFGIEPNAE LIYEVTLKSF
260 270 280 290 300
EKAKESWEMD TKEKLEQAAI VKEKGTVYFK GGKYMQAVIQ YGKIVSWLEM
310 320 330 340 350
EYGLSEKESK ASESFLLAAF LNLAMCYLKL REYTKAVECC DKALGLDSAN
360 370 380 390 400
EKGLYRRGEA QLLMNEFESA KGDFEKVLEV NPQNKAARLQ ISMCQKKAKE
410 420 430 440 450
HNERDRRIYA NMFKKFAEQD AKEEANKAMG KKTSEGVTNE KGTDSQAMEE

EKPEGHV
Length:457
Mass (Da):51,212
Last modified:July 15, 1998 - v2
Checksum:i18A86608C6891A73
GO
Isoform 2 (identifier: Q13451-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     223-268: YGFGEAGKPK...MDTKEKLEQA → PKNPGRWIPK...SISKNLFKCW
     269-457: Missing.

Note: No experimental confirmation available.
Show »
Length:268
Mass (Da):30,032
Checksum:i2B172A6E03570AAD
GO

Sequence cautioni

The sequence BAD93130 differs from that shown. Reason: Frameshift at position 29. Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei223 – 26846YGFGE…KLEQA → PKNPGRWIPKKNWSRLPLSK RREPYTSRCVSPYAILSISK NLFKCW in isoform 2. 1 PublicationVSP_044820Add
BLAST
Alternative sequencei269 – 457189Missing in isoform 2. 1 PublicationVSP_044821Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U71321 mRNA. Translation: AAC51189.1.
AF194172 mRNA. Translation: AAL54872.1.
AK312422 mRNA. Translation: BAG35332.1.
AB209893 mRNA. Translation: BAD93130.1. Frameshift.
AL033519 Genomic DNA. Translation: CAI20256.1.
AL157823 Genomic DNA. No translation available.
AL590400 Genomic DNA. No translation available.
CH471081 Genomic DNA. Translation: EAX03842.1.
BC042605 mRNA. Translation: AAH42605.1.
U42031 mRNA. Translation: AAA86245.1.
CCDSiCCDS4808.1. [Q13451-1]
CCDS54996.1. [Q13451-2]
PIRiJC5422.
RefSeqiNP_001139247.1. NM_001145775.2. [Q13451-1]
NP_001139248.1. NM_001145776.1. [Q13451-1]
NP_001139249.1. NM_001145777.1. [Q13451-2]
NP_004108.1. NM_004117.3. [Q13451-1]
UniGeneiHs.407190.

Genome annotation databases

EnsembliENST00000357266; ENSP00000349811; ENSG00000096060. [Q13451-1]
ENST00000536438; ENSP00000444810; ENSG00000096060. [Q13451-1]
ENST00000539068; ENSP00000441205; ENSG00000096060. [Q13451-1]
ENST00000542713; ENSP00000442340; ENSG00000096060. [Q13451-2]
GeneIDi2289.
KEGGihsa:2289.
UCSCiuc003okx.3. human. [Q13451-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U71321 mRNA. Translation: AAC51189.1.
AF194172 mRNA. Translation: AAL54872.1.
AK312422 mRNA. Translation: BAG35332.1.
AB209893 mRNA. Translation: BAD93130.1. Frameshift.
AL033519 Genomic DNA. Translation: CAI20256.1.
AL157823 Genomic DNA. No translation available.
AL590400 Genomic DNA. No translation available.
CH471081 Genomic DNA. Translation: EAX03842.1.
BC042605 mRNA. Translation: AAH42605.1.
U42031 mRNA. Translation: AAA86245.1.
CCDSiCCDS4808.1. [Q13451-1]
CCDS54996.1. [Q13451-2]
PIRiJC5422.
RefSeqiNP_001139247.1. NM_001145775.2. [Q13451-1]
NP_001139248.1. NM_001145776.1. [Q13451-1]
NP_001139249.1. NM_001145777.1. [Q13451-2]
NP_004108.1. NM_004117.3. [Q13451-1]
UniGeneiHs.407190.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1KT0X-ray2.70A1-457[»]
3O5DX-ray4.00A/B1-260[»]
3O5EX-ray1.60A1-140[»]
3O5FX-ray1.65A1-140[»]
3O5GX-ray2.00A16-140[»]
3O5IX-ray1.80A/B16-140[»]
3O5JX-ray1.70A16-140[»]
3O5KX-ray2.70A/B/C/D16-140[»]
3O5LX-ray1.30A16-140[»]
3O5MX-ray1.60A/B16-140[»]
3O5OX-ray1.15A16-140[»]
3O5PX-ray1.00A16-140[»]
3O5QX-ray0.96A16-140[»]
3O5RX-ray1.10A16-140[»]
4DRHX-ray2.30A/D1-140[»]
4DRIX-ray1.45A1-140[»]
4DRKX-ray1.50A/B16-140[»]
4DRMX-ray1.48A16-140[»]
4DRNX-ray1.07A16-140[»]
4DROX-ray1.10A16-140[»]
4DRPX-ray1.80A16-140[»]
4DRQX-ray1.00A16-140[»]
4JFIX-ray1.05A16-139[»]
4JFJX-ray1.08A16-140[»]
4JFKX-ray1.15A16-140[»]
4JFLX-ray1.20A16-140[»]
4JFMX-ray1.02A16-140[»]
4R0XX-ray1.20A20-140[»]
4TW6X-ray1.40A16-140[»]
4TW7X-ray1.25A16-140[»]
4TX0X-ray1.03A16-140[»]
4W9OX-ray1.27A/E16-140[»]
4W9PX-ray1.50A/E16-140[»]
4W9QX-ray1.08A16-140[»]
5BXJX-ray1.24A16-140[»]
5DITX-ray2.25A16-140[»]
5DIUX-ray1.30A16-140[»]
5DIVX-ray1.65A16-139[»]
ProteinModelPortaliQ13451.
SMRiQ13451. Positions 13-412.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108579. 106 interactions.
DIPiDIP-27597N.
IntActiQ13451. 117 interactions.
MINTiMINT-1142816.
STRINGi9606.ENSP00000338160.

Chemistry

BindingDBiQ13451.
ChEMBLiCHEMBL2052031.

PTM databases

iPTMnetiQ13451.
PhosphoSiteiQ13451.
SwissPalmiQ13451.

Polymorphism and mutation databases

BioMutaiFKBP5.
DMDMi2851536.

Proteomic databases

EPDiQ13451.
PaxDbiQ13451.
PeptideAtlasiQ13451.
PRIDEiQ13451.

Protocols and materials databases

DNASUi2289.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000357266; ENSP00000349811; ENSG00000096060. [Q13451-1]
ENST00000536438; ENSP00000444810; ENSG00000096060. [Q13451-1]
ENST00000539068; ENSP00000441205; ENSG00000096060. [Q13451-1]
ENST00000542713; ENSP00000442340; ENSG00000096060. [Q13451-2]
GeneIDi2289.
KEGGihsa:2289.
UCSCiuc003okx.3. human. [Q13451-1]

Organism-specific databases

CTDi2289.
GeneCardsiFKBP5.
HGNCiHGNC:3721. FKBP5.
HPAiCAB009315.
HPA031092.
HPA031093.
HPA031095.
MalaCardsiFKBP5.
MIMi602623. gene.
neXtProtiNX_Q13451.
PharmGKBiPA28162.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0543. Eukaryota.
COG0545. LUCA.
GeneTreeiENSGT00760000119159.
HOGENOMiHOG000256916.
HOVERGENiHBG051624.
InParanoidiQ13451.
KOiK09571.
OMAiVCHLLCK.
OrthoDBiEOG091G07OA.
PhylomeDBiQ13451.
TreeFamiTF105292.

Miscellaneous databases

ChiTaRSiFKBP5. human.
EvolutionaryTraceiQ13451.
GeneWikiiFKBP5.
GenomeRNAii2289.
PROiQ13451.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000096060.
CleanExiHS_FKBP5.
GenevisibleiQ13451. HS.

Family and domain databases

Gene3Di1.10.150.160. 1 hit.
1.25.40.10. 1 hit.
InterProiIPR023114. Elongated_TPR_rpt_dom.
IPR031210. FKBP5.
IPR023566. PPIase_FKBP.
IPR001179. PPIase_FKBP_dom.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR001440. TPR_1.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR10516. PTHR10516. 2 hits.
PTHR10516:SF26. PTHR10516:SF26. 2 hits.
PfamiPF00254. FKBP_C. 2 hits.
PF00515. TPR_1. 1 hit.
PF13181. TPR_8. 1 hit.
[Graphical view]
SMARTiSM00028. TPR. 2 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 1 hit.
PROSITEiPS50059. FKBP_PPIASE. 2 hits.
PS50005. TPR. 3 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFKBP5_HUMAN
AccessioniPrimary (citable) accession number: Q13451
Secondary accession number(s): F5H7R1, Q59EB8, Q5TGM6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 15, 1998
Last modified: September 7, 2016
This is version 168 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.